The overall long-term goal of these studies is to understand the mechanisms by which pulmonary blood flow is controlled, and how that control contributes to gas exchange defects or optimization in health and disease. The specific goal is to use a novel MRI technique to quantify the spatial and temporal dynamics of blood flow in the normal human lung. Temporal heterogeneity in a number of physiological systems has been found to be a mark of healthy function, yet little is known about the temporal dynamics of blood flow in the human lung because the appropriate tools for measuring temporal heterogeneity have not been available. Recently we developed a noninvasive MRI technique that provides quantitative measurements of pulmonary blood flow with a spatial resolution of ~1 cm3 and a temporal resolution of ~10 s in the human lung permitting us to examine spatial-temporal heterogeneity in the human lung for the first time. Under the umbrella of this project, the Specifi Aims are designed to: 1) provide the fellow with training in the development of MRI techniques, with a goal of improving the temporal resolution in these studies; 2) to develop innovative analysis techniques including aspects of non-linear systems to characterize the rich data sets resulting from our experimental techniques; and 3) examine the effects of altered inspired gas (O2 and CO2) in healthy subjects. PUBLIC HEALTH RELEVANCE: The overall long-term goal of these studies is to understand the mechanisms by which pulmonary blood flow is controlled, and how that control contributes to gas exchange defects or optimization in health and disease. The importance of how pulmonary blood flow is controlled over time has never been studied in humans because of a lack of suitable tools. This project will study the temporal behavior of the distribution of pulmonary blood flow in humans for the first time laying the foundations for addressing future treatment of gas exchange defects.